Low-Dose Mifepristone Regimens Are Effective And Safe for Early Abortion

Medication abortion regimens consisting of 200 mg of mifepristone followed by misoprostol are highly effective and safe during early pregnancy, according to an analysis of pooled data from 87 prospective trials.1 Treatment failure occurred in 5% of the 45,000 women with evaluable data; ongoing pregnancy occurred in 1%. The odds of medication abortion failure were higher in trial groups in which at least 25% of women were more than eight weeks’ pregnant than in groups with a lower proportion of such women (odds ratio, 1.5), and higher in groups taking misoprostol less than 23 hours after mifepristone administration than in those instructed to take it 23–72 hours after receiving mifepristone (2.1).

Although 600 mg of mifepristone followed by misoprostol is specified in most medication abortion regimens approved by government regulatory agencies worldwide, a 200-mg dose of mifepristone is widely used. Moreover, standards for the dose, route and timing of misoprostol have not been established. In the current analysis, researchers compiled existing data on the safety and effectiveness of medication abortion regimens consisting of 200 mg of mifepristone followed by misoprostol and used logistic regression to examine the associations between trial and population characteristics and abortion failure and ongoing pregnancy.

The data, collected at 314 sites in 35 countries (including more than a dozen developing nations), come from 87 published and unpublished trials in which at least one group of women was treated with an abortion regimen consisting of 200 mg of mifepristone followed by misoprostol. The majority of the trials were conducted between 1994 and 2011 (24 did not report data collection dates); 36 were randomized and 51 were prospective cohort or case series studies. Data on ongoing pregnancies were reported for 117 of the 120 study groups. For each trial, the researchers abstracted information on the study design, treatment protocol, number of women, participant characteristics, and the numbers of abortion failures, ongoing pregnancies, hospitalizations and blood transfusions. The analyses were limited to women who had received mifepristone, had had a gestational age of up to 63 days, had not had an ectopic pregnancy and had had a known abortion outcome.

The prescribed dose of misoprostol in the study regimens ranged from 200 to 6,400 mcg; in most cases, the drug was given in one dose, but in 13 groups women received divided doses over 1–7 days. Misoprostol was administered vaginally, orally, buccally or sublingually; most commonly, women received 800 mcg of misoprostol vaginally or 400 mcg orally. The time between mifepristone and misoprostol administration was 0–72 hours, and while some protocols required women to take misoprostol in the clinic, others allowed all or most women to take it at home. Abortion outcomes were evaluated 1–21 days after administration of mifepristone; in half of the trial groups, ultrasound was used to determine the regimen’s success. In all, outcome data were available for 45,528 women.

Medication abortion failure occurred in 5% of cases; across trial groups, this percentage ranged from 0% to 40%. Half of all trial groups had failure rates below 5%, and more than 90% of women were in groups with failure rates below 9%. One percent of women had ongoing pregnancies; more than 90% were in trial groups in which fewer than 3% of women reported ongoing pregnancies. Across all trial groups, 0.3% of women were hospitalized and 0.1% received blood transfusions; hospitalizations and transfusions were less common in trials in which women could take misoprostol at home than in trials requiring misoprostol administration in the clinic.

Multivariate analyses revealed that the odds of medication abortion failure were ele-vated in trial groups in which at least 25% of women were more than eight weeks pregnant, compared with groups in which fewer than 25% of women were more than eight weeks pregnant (odds ratio, 1.5). The odds of abortion failure were also higher in groups that took misoprostol less than 23 hours after mifepristone administration than in groups that took it 23–72 hours after mifepristone (2.1). At most misoprostol dose levels (400 mcg, 600 mcg and ≥800 mcg), the odds of abortion failure were lower with vaginal, buccal and sublingual administration than with oral administration (0.2–0.6); the likelihood of failure did not differ among women receiving vaginal, buccal or sublingual administration. For oral and vaginal administration, abortion failure was less likely at misoprostol doses of 800 mcg or higher than at doses of 400 mcg (0.6–0.7); for sublingual administration, a dose of 600 mcg was associated with lower odds of medication abortion failure than a dose of 400 mcg (0.3). In general, the associations between misoprostol dose and route and ongoing pregnancy were similar to those for medication abortion failure of any type. Rates of abortion failure rate and ongoing pregnancy were similar across geographic regions (classified as Europe, the Americas or other).

The authors cite a number of limitations, some of which were related to the nature of the studies examined. For example, the data permitted exploration of heterogeneity across patient populations, but not among individual patients, and the researchers were unable to control for unmeasured confounding by randomization. Nonetheless, given that an abundance of research “conducted in disparate settings over nearly two decades using a variety of regimens and treatment protocols” demonstrates the effectiveness of 200-mg mifepristone regimens, the authors suggest that future explorations “focus on service delivery issues: increasing access, reducing cost, enhancing patient comfort and ensuring availability of ancillary services such as contraception that can aid women in reaching their reproductive goals.”—L. Melhado